Autor: |
Jun Suzuki, Tomotaka Hemmi, Masamitsu Maekawa, Masahiro Watanabe, Hitoshi Inada, Hiroyuki Ikushima, Tetsuya Oishi, Ryoukichi Ikeda, Yohei Honkura, Yoshiteru Kagawa, Tetsuaki Kawase, Nariyasu Mano, Yuji Owada, Noriko Osumi, Yukio Katori |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Scientific Reports, Vol 13, Iss 1, Pp 1-15 (2023) |
Druh dokumentu: |
article |
ISSN: |
2045-2322 |
DOI: |
10.1038/s41598-023-48702-4 |
Popis: |
Abstract Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL. |
Databáze: |
Directory of Open Access Journals |
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